en
Scientific article
Open access
English

Prognostic and therapeutic considerations of antibodies against c‐ter apolipoprotein A‐1 in the general population

Published inClinical & translational immunology, vol. 9, no. 12, e1220
Publication date2020-12-14
First online date2020-12-14
Abstract

Objectives: Autoantibodies against apolipoprotein A1 (anti-apoA1 IgGs) and its C-terminal region (cter apoA1) have emerged as an independent biomarker for cardiovascular disease. Cter apoA1 mimetic peptides were shown to reverse the deleterious anti-apoA1 IgG effects in vitro. We evaluated the association of anti-cter apoA1 IgGs with overall mortality in the general population and tested the ability of a cter apoA1 mimetic peptide to reverse the anti-apoA1 IgG-induced inflammatory response and mortality in vitro and in vivo, respectively.

Methods: Anti-cter apoA1 IgGs were measured in serum samples of 6386 participants of the CoLaus study of which 5220 were followed for a median duration of 5.6 years. The primary outcome was overall mortality. The peptide inhibitory concentration 50% (IC50) was determined in vitro on HEK-Blue-4 and RAW cells. ApoE-/- mice were exposed to 16 weeks of anti-apoA1IgG passive immunisation with and without peptide co-incubation.

Results: Anti-cter apoA1 IgGs were associated with higher interleukin 6 levels and independently predicted overall mortality; an increase of one standard deviation of anti-cter apoA1 IgG level was associated with an 18% increase in mortality risk (hazard ratio: 1.18, 95% confidence interval: 1.04-1.33; P = 0.009). The cterApoA1 analogue reversed the antibody-mediated inflammatory response with an IC50 of 1 µm in vitro but did not rescue the significant anti-apoA1 IgG-induced mortality rate in vivo (69% vs. 23%, LogRank P = 0.02).

Conclusion: Anti-cter apoA1 IgG independently predicts overall mortality in the general population. Despite being effective in vitro, our cter apoA1 analogue did not reverse the anti-apoA1 IgG-induced mortality in mice. Our data suggest that these autoantibodies are not readily treatable through cognate peptide immunomodulation.

eng
Keywords
  • ApoE−/− mice
  • CoLaus study
  • C‐terminal A1 peptide
  • Anti‐apoA‐1 IgG
  • Passive immunisation
Funding
Citation (ISO format)
VUILLEUMIER, Nicolas et al. Prognostic and therapeutic considerations of antibodies against c‐ter apolipoprotein A‐1 in the general population. In: Clinical & translational immunology, 2020, vol. 9, n° 12, p. e1220. doi: 10.1002/cti2.1220
Main files (1)
Article (Published version)
Secondary files (1)
Identifiers
ISSN of the journal2050-0068
107views
56downloads

Technical informations

Creation11/23/2021 10:20:00 AM
First validation11/23/2021 10:20:00 AM
Update time03/16/2023 2:39:48 AM
Status update03/16/2023 2:39:47 AM
Last indexation05/06/2024 9:55:50 AM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack